Non-steroidal anti-inflammatory drugs (NSAIDS) are routinely used in the treatment of arthritis and sports injuries. They are also very effective at controlling fevers.
Scientists at the National Institute for Cellular Biotechnology at Dublin City University have discovered another use for these drugs.
NSAIDS could make resistant cancer cells more susceptible to chemotherapy drugs. The university is now collaborating with St Vincent's Hospital in a drug trial that could lead to new cancer treatments.
Some patients being treated for cancer of the lung, colon and breast are either resistant to chemotherapy or develop resistance to commonly used anti-cancer drugs. This is caused by high levels inside the cancer cells of a protein called multidrug resistant associated protein, MRP-I. The protein sits on the surface of a cell and acts like a pump, pushing the cancer drugs back out of the cell before they can have an effect.
The normal purpose of the protein pump is to prevent toxins or foreign chemicals from invading healthy cells. In the case of chemotherapy drugs, the pump recognises them as powerful toxins and so sets to work repelling them from the cell.
"We have been studying the mechanisms of the MRP-I protein in order to identify the drugs that will block its pumping mechanism," said Prof Martin Clynes, director of the institute.
The researchers tried antibiotics and NSAID aspirin before achieving success with a small number of other NSAIDS. These will now be used to test if administration of a NSAID with chemotherapy can improve treatments for the patient.
The well-established anti-inflammatory drug, Sulindac, will be used in a phase I trial. This will aim to ensure low toxicity and safety when given in combination with the standard chemotherapy drug, Epirubicin.
Patients will be recruited at St Vincent's Hospital, Dublin, using a clinical protocol approved by the Irish Medicines Board. Oncologist Dr John Crown and his team will recruit up to 25 patients over the coming 18 months in phase I of the trial.
If this goes well, drug combinations will be tested on a much larger number of patients to see if they improve survival from cancer. This will involve close collaboration between surgeons, Mr Vincent Lynch, Mr Arnold Hill and Mr Enda McDermott; pathologist Dr Susan Kennedy and Professor Clynes and his team, who will examine tissue biopsies before patients receive their chemotherapy.
By determining the levels of MRP-I in advance, doctors should be able to target the combined NSAIDS/chemotherapy regime at those who will benefit most.
Prof Clynes warned that they were at least five years away from completing all phases of the clinical trials. "Even then, this intervention might benefit, at most, five to 10 per cent of cancer patients." The research is being funded by the Dublin City University Educational Trust, The Health Research Board and The Irish Cancer Society. It is unusual in that the new cancer treatment is being developed entirely within the State, from basic discovery, through development and into clinical trials.